Increased plasma von Willebrand factor in the systemic inflammatory response syndrome is derived from generalized endothelial cell activation.
OBJECTIVE
Von Willebrand factor antigen (vWf) is an essential hemostatic protein. Increased plasma levels have been documented in patients suffering from the systemic inflammatory response syndrome (SIRS) and resulted presumably from endothelial cell damage specific to the site of injury. We hypothesize that increased plasma levels result from systemic endothelial cell activation and degranulation.


METHODS
We compared immunohistochemical vWf staining in dermal biopsy specimens from patients with SIRS to healthy control subjects in the presence and absence of recombinant human tumor necrosis factor (rhTNF)-alpha. Also, we quantified plasma levels of vWf in these groups using a newly available antibody.


METHODS
A tertiary care surgical intensive care unit in a university teaching hospital.


METHODS
Patients with SIRS and healthy controls.


METHODS
Biopsies and blood samples were obtained from study groups.


RESULTS
Decreased baseline vWf staining was noted in SIRS patients. The rhTNF-alpha caused a statistically significant decrease in vWf staining in control subjects but not in SIRS patients. Plasma vWf levels were increased an average of 11-fold in SIRS patients compared with control subjects.


CONCLUSIONS
We postulate that the increased plasma levels of vWf and the decreased staining in the peripheral dermal plexus represent the generalized activation and degranulation of endothelium in vascular beds remote from the original inflammatory focus.
McGill
S N
SN
Queen's University, Kingston, ON, Canada.
Ahmed
N A
NA
Christou
N V
NV
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D016638:Critical Illness; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007271:Injections, Intradermal; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage; D012867:Skin / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage; D014841:von Willebrand Factor / Q000032:analysis* / Q000187:drug effects
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014841:von Willebrand Factor